Nicotinic acetylcholine receptors in the brain

Abstract

The nicotinic acetylcholine receptor (nAChR) is the archetypal neurotransmitter receptor within the superfamily of pentameric ligand-gated ion channels (pLGICs). Typically, it mediates fast synaptic transmission in response to its endogenous ligand, acetylcholine, and can also intervene in slower signaling mechanisms via intracellular metabolic cascades in association with G-protein-coupled receptors. This review covers the structural and functional aspects of the different neuronal nAChR subtypes and their cellular and anatomic distribution in the brain. The significant progress in our knowledge on the topic derives from the successful combination of biochemical, neuroanatomic, pharmacologic, and cell biology approaches, complemented by site-directed mutagenesis, single-channel electrophysiology, and structural biophysical studies. This multipronged approach provides a comprehensive description of nAChR in health and disease, offering improved chances of success in tackling neurologic and neuropsychiatric diseases involving phenotypic alterations of nAChRs, particularly in neurodegenerative diseases.